Calcitonin prevents bone loss but decreases osteoblastic activity in ovariohysterectomized beagle dogs
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Abstract The antiresorptive effects of calcitonin are well documented. Recent in vitro and in vivo evidence points to an anabolic effect of calcitonin on osteoblasts. To assess the value of calcitonin in preventing the rapid and early bone loss after cessation of ovarian function and to investigate its effects on osteoblasts in vivo, 32 dogs were ovariohysterectomized (OHX) and 32 dogs were sham-operated (Sham). After the surgeries, half of the OHX and Sham dogs received every-other-day subcutaneous injections of human calcitonin (0.25 mg/dog/d), and the remaining dogs were given vehicle. Half of the animals had a bone biopsy at week 2 and were euthanized thereafter; the other half of the animals underwent a bone biopsy at month 1 and were euthanized at month 4. Blood drawings were done at baseline and at the time of each bone biopsy. Calcitonin prevented the increase in erosion depth seen in OHX animals and prevented the cancellous bone loss observed at 2 weeks and at 1 and 4 months. Calcitonin did not affect bone volume in Sham dogs. However, treatment with calcitonin induced a decrease in mineralizing surfaces and bone formation rates at the bone surface and cell level and an increase in mineralization lag time in both Sham and OHX animals without significantly affecting osteoblast number. This finding indicates that the negative effect of calcitonin on bone mineralization is not solely the result of a decrease in bone turnover. The data show that calcitonin, because of its antiresorptive effects, can prevent bone loss after cessation of ovarian function. However, short-term treatment with calcitonin does not stimulate osteoblast activity; on the contrary, it exerts a negative effect on osteoblastic bone formation and mineralization. Long-term studies are needed to investigate whether this unwanted effect of calcitonin on osteoblasts in vivo represents a transitory or persistent phenomenon.Keywords:
Bone remodeling
Beagle
Cancellous bone
We identified the presence of Renaut bodies in an unusual location in Beagle dogs on a 3-month nonclinical toxicity study. These peculiar structures are commonly reported as a background finding in the sciatic nerve of dogs. In our study, however, they were also observed in autonomic nerves surrounding the adrenal gland, a location in which they have not been reported before. The incidence in both locations were 8 of 32 Beagle dogs in the sciatic nerve and 6 of 40 Beagle dogs around the adrenal gland in the dosing and/or recovery phases of the study.
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Objective To obtain the basic data of physiological and biochemical characteristics of Beagle dog's blood which are in different sex and age,and the weight of main organs and their coefficient of 8～12 months beagle dogs were measured,for pharmaceutical and toxicological experimental references.Methods Blood samples were taken from over 3000 Beagle dogs of different age and sex.Physiological and biochemical characteristics were examined by HITACHI-7020 automatic chemistry analyzer and SWELAB-AC920EO automatic hematology analyzer.The weight of main organs and their coefficient of 128 beagle dogs were measured.Results and Conclusion Basic data of physiological and biochemical characteristics of different sex and age,and the weight of main organs and their coefficient of Beagle dog's were obtained.
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Objective To obtain the basic data of biological parameters of Beagle.Methods Routine methods and instrument are used to determine the biological parameters in Beagle using BECKMAN SYNCHRON CX5 PRO.ResultsThere were a few significant differences in Beagle between sexes(male and female Beagle)on parameters of CHOL、TG.Other indexes were no significant differences.ConclusionThere were no significant differences of some biological parameters in different sex and age.The all indexes were relatively stabilization.
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AIM: To set up a sensitive and rapid high performance liquid chromatography (HPLC) method to determine MN9202 and to study its pharmacokinetics in Beagle dogs. METHODS: The mobile phase and extraction methods were optimized by the orthogonal experimental design. MN9202 was intravenously administered to the Beagle dogs at the dose of 0.335 mg/kg and MN9202 in plasma was detected by HPLC. The pharmacokinetic parameters were calculated by 3P97 software. RESULTS: Under the selected HPLC conditions, the MN9202 was clearly separated from interference and the retention time of MN9202 was less than 14 min. When MN9202 was intravenously administered, the plasma concentration-time curve was fit to two-compartment model. T 1/2 β was (200±32) min. and AUC was (32 147± 9544)μg·min/L. CONCLUSION: The analytical method we set up is simple, sensitive and accurate, and it can be applied to determine the MN9202 in the plasma of Beagle dogs. The speed of elimination of MN9202 is high in Beagle dogs.
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Aim To determine the pharmacokinetics features of peperphentonamine(PPTA) in beagle dogs.Methods Following a single iv administration with different doses of PPTA to beagle dogs(2.63,5 and 10mg.kg-1),the blood samples were collected at different time after treatment and the concentration of PPTA in plasma were determined by HPLC-UV method.Results The pharmacokinetic parameters of PPTA after single iv administration of PPTA 2,4 and 8 mg.kg-1 in beagle dogs were follows:AUC were 4905 ± 1421、10253 ± 3616、24256 ± 5471 ng.min.mL-1,t1/2 were 0.76 ± 0.10、1.26 ± 0.46、1.32 ± 0.35 min,respectively.Conclusion It was shown that the plasma concentration-time data was fit to a double compartment pharmacokinetic model in beagle dogs after iv administra-tion and the elimination of PPTA was found to be in according with linear kinetics characteristics.
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Bone strength is maintained by repeated bone resorption and formation. This metabolic activity is regulated by both biochemical factors, such as intercellular signaling, and mechanical factors, such as mechanosensing by osteocytes. We constructed a mathematical model of bone metabolism considering both biochemical and mechanical factors. In addition, we created a simulation model of cancellous bone based on X-ray micro CT images of a mouse femur. By using the constructed mathematical model and the cancellous bone model, we performed bone metabolism/remodeling simulation for cancellous bone under the same condition as a previous experiment using mice. The cancellous bone structure obtained by the remodeling simulation was quantitatively in agreement with the previous by reported experimental results. Through this comparison, we showed that the constructed simulator has a potential to quantitatively reproduce cancellous bone structure observed in mouse experiments.
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Aim To study the pharmacokinetics of Levofloxacin(LVFX) in beagle dogs. Methods Four Beagle dogs were administered with a single dose of LVFX(25mg·kg-1) by intravenous infusion(for 60min). Plasma concentration of LVFX in Beagle dogs was determined by RP-HPLC. The pharmacokinetic parameters of LVFX in Beagle dogs were calculated by 3P97 software. Results The plasma concentration-time curve of LVFX in Beagle dogs confomed to a two-compartment model. Pharmacokintic parameters were t1/2β(8.23±0.65)h,Vc(7.47±3.13)L,AUC (247.00±14.10)mg· h·L-1,Cmax (30.05±1.75)mg· L-1,respectively. Conclusion Pharmacokinetic characteristics of LVFX in Beagle dogs were similar with those of humans.
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To obtain the basic data of physiological Beagle dog's blood for experimental references,Beagle dogs were measured by physiological analyzer. And normal reference values of body temperature,respiration,blood pressure,heart rate,and other physiological indexes of were obtained. The data in this research could provide reference for Beagle dogs' experiments.
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A newly developed assay for hydroxyproline (Hyp) in physiological samples was used for determining the biological variations in serum total Hyp in the beagle dog. The results showed that dietary Hyp restriction in the beagle dog results in a significant decrease in serum total Hyp over the first 24 h and that there are no obvious circadian variations in serum total Hyp concentrations in beagle dogs on dietary Hyp restriction.
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